tbuckley/cabot-search huggingface dataset:
Intrathecal trastuzumab: What else do we need to consider?
Authors: Tianqi Gao, Shaoqiong Zhang, Man Li
Journal: Neuro-Oncology (2022)

Journal Article Intrathecal trastuzumab: What else do we need to consider? Get access Tianqi Gao, Tianqi Gao Department of Oncology, The Second Hospital of Dalian Medical University, Dalian, China Search for other works by this author on: Oxford Academic PubMed Google Scholar Shaoqiong Zhang, Shaoqiong Zhang Department of Anesthesiology, The First Hospital of China Medical University, Shenyang, China Search for other works by this author on: Oxford Academic PubMed Google Scholar Man Li Man Li Department of Oncology, The Second Hospital of Dalian Medical University, Dalian, China Corresponding Author: Man Li, MD, PhD, Department of Oncology, The Second Hospital of Dalian Medical University, No. 467 Zhongshan Road, Dalian, Liaoning 116023, China (man_li@dmu.edu.cn). Search for other works by this author on: Oxford Academic PubMed Google Scholar Neuro-Oncology, Volume 25, Issue 2, February 2023, Pages 418–419, https://doi.org/10.1093/neuonc/noac225 Published: 19 December 2022 Article history Corrected and typeset: 19 December 2022 Published: 19 December 2022
Therapy for Stage IV Non–Small-Cell Lung Cancer Without Driver Alterations: ASCO Living Guideline, Version 2022.2
Authors: Dwight H. Owen, Navneet Singh, Nofisat Ismaila, Elizabeth Blanchard, Paul Celano, Narjust Florez, Dharamvir Jain, Natasha B. Leighl, Hirva Mamdani, Gregory Masters, Pamela R. Moffitt, Jarushka Naidoo, Tanyanika Phillips, Gregory J. Riely, Andrew G. Robinson, Erin Schenk, Bryan J. Schneider, Lecia Sequist, David R. Spigel, Ishmael A. Jaiyesimi
Journal: Journal of Clinical Oncology (2022)

Living guidelines are developed for selected topic areas with rapidly evolving evidence that drives frequent change in recommended clinical practice. Living guidelines are updated on a regular schedule by a standing expert panel that systematically reviews the health literature on a continuous basis, as described in the ASCO Guidelines Methodology Manual. ASCO Living Guidelines follow the ASCO Conflict of Interest Policy Implementation for Clinical Practice Guidelines. Living Guidelines and updates are not intended to substitute for independent professional judgment of the treating provider and do not account for individual variation among patients. See Appendix 1 (online only) for disclaimers and other important information. Updates are published regularly and can be found at https://ascopubs.org/nsclc-non-da-living-guideline.
Partial endothelial-to-mesenchymal transition mediated by HIF-induced CD45 in neointima formation upon carotid artery ligation
Authors: Yoshito Yamashiro, Karina Ramirez, Kazuaki Nagayama, Naoko Hattori, Yu-Yu Liu, Shinji Matsunaga, Shuhei Tomita, Yoshiaki Kubota, Hiromi Yanagisawa
Journal: Cardiovascular Research (2022)

Endothelial-to-mesenchymal transition (EndMT) is a fundamental process in vascular remodelling. However, the precise regulatory mechanism of vascular remodelling during neointima formation and the source of neointima cells are not entirely understood.To investigate the origin of neointima cells and their relevance to vascular wall remodelling, we used an endothelial cell (EC)-specific lineage tracing system [VE-Cadherin (Cdh5)-BAC-CreERT2 mice] and carotid artery ligation model and showed evidence that resident ECs transdifferentiate into neointima cells with the expression of CD45. During the early stages of neointima formation, ECs transiently expressed CD45, a haematopoietic marker, accompanied by a host of EndMT markers, and CD31 and αSMA were prominently expressed in developing neointima. In vitro, CD45-positive EndMT was induced by stabilization of HIF1α with cobalt chloride or with a VHL inhibitor in human primary ECs, which mimicked the hypoxic condition of the ligated artery, and promoted the formation of an integrin α11-shank-associated RH domain-interacting protein (SHARPIN) complex. Notably, a CD45 phosphatase inhibitor disrupted this integrin α11-SHARPIN complex, thereby destabilizing cell-cell junctions. Deletion of Hif1α in ECs suppressed expression of CD45 and EndMT markers and ameliorated neointima formation.These results suggest that the HIF-induced CD45 expression is normally required for the retention of an EC fate and cell-cell junctions, CD45-positive EndMT (termed as 'partial EndMT') contributes to neointima formation and vascular wall remodelling.
Durvalumab with or without tremelimumab versus the EXTREME regimen as first-line treatment for recurrent or metastatic squamous cell carcinoma of the head and neck: KESTREL, a randomized, open-label, phase III study
Authors: A. Psyrri, J. Fayette, K. Harrington, M. Gillison, M.-J. Ahn, S. Takahashi, J. Weiss, J.-P. Machiels, S. Baxi, A. Vasilyev, A. Karpenko, M. Dvorkin, C.-Y. Hsieh, S.C. Thungappa, P.P. Segura, I. Vynnychenko, R. Haddad, S. Kasper, P.-S. Mauz, V. Baker, P. He, B. Evans, S. Wildsmith, R.F. Olsson, A. Yovine, J.F. Kurland, N. Morsli, T.Y. Seiwert
Journal: Annals of Oncology (2022)

Patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) have a poor prognosis. The phase III KESTREL study evaluated the efficacy of durvalumab [programmed death-ligand 1 (PD-L1) antibody] with or without tremelimumab [cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) antibody], versus the EXTREME regimen in patients with R/M HNSCC.
Genetic Modeling of B-cell State Transitions for Rational Design of Lymphoma Therapies
Authors: Etienne Leveille, Shalin Kothari, Markus Müschen
Journal: Blood Cancer Discovery (2022)

Summary: The use of genomic data to analyze primary endpoints for clinical trials in diffuse large B-cell lymphomas (DLBCL) significantly improved the development of rational drug combinations for genetically defined patient subsets. Recent genetic mouse models and their ability to recapitulate transitions between germinal center exit and memory B-cell characteristics in DLBCL will accelerate the development of rationale-based clinical trials. See related article by Flümann et al., p. 78 (3). See related article by Venturutti et al., (5).
Aging-associated HELIOS deficiency in naive CD4+ T cells alters chromatin remodeling and promotes effector cell responses
Authors: Huimin Zhang, Rohit R. Jadhav, Wenqiang Cao, Isabel N. Goronzy, Tuantuan V. Zhao, Jun Jin, Shozo Ohtsuki, Zhaolan Hu, Jose Morales, William J. Greenleaf, Cornelia M. Weyand, Jörg J. Goronzy
Journal: Nature Immunology (2022)
A Small Change With a Twist Ending: A Single Residue in EGF-CFC Drives Bilaterian Asymmetry
Authors: Marta Truchado-García, Kimberly J Perry, Florencia Cavodeassi, Nathan J Kenny, Jonathan Q Henry, Cristina Grande
Journal: Molecular Biology and Evolution (2022)

Asymmetries are essential for proper organization and function of organ systems. Genetic studies in bilaterians have shown signaling through the Nodal/Smad2 pathway plays a key, conserved role in the establishment of body asymmetries. Although the main molecular players in the network for the establishment of left-right asymmetry (LRA) have been deeply described in deuterostomes, little is known about the regulation of Nodal signaling in spiralians. Here, we identified orthologs of the egf-cfc gene, a master regulator of the Nodal pathway in vertebrates, in several invertebrate species, which includes the first evidence of its presence in non-deuterostomes. Our functional experiments indicate that despite being present, egf-cfc does not play a role in the establishment of LRA in gastropods. However, experiments in zebrafish suggest that a single amino acid mutation in the egf-cfc gene in at least the common ancestor of chordates was the necessary step to induce a gain of function in LRA regulation. This study shows that the egf-cfc gene likely appeared in the ancestors of deuterostomes and "protostomes", before being adopted as a mechanism to regulate the Nodal pathway and the establishment of LRA in some lineages of deuterostomes.
Molecular heterogeneity of pediatric choroid plexus carcinomas determines the distinctions in clinical course and prognosis
Authors: Margarita Zaytseva, Andge Valiakhmetova, Ludmila Yasko, Alexey Samarin, Ludmila Papusha, Anastasia Shekhtman, Natalia Usman, Kirill Voronin, Alexander Karachunskiy, Galina Novichkova, Alexander Druy
Journal: Neuro-Oncology (2022)

Choroid plexus carcinomas (CPCs) are rare aggressive pediatric tumors of the brain with no treatment standards. Genetic profiling of CPCs is often confined to possible association with Li-Fraumeni syndrome, though only about a half of CPCs develop from syndromic predispositions. Whole-chromosome gains and losses typical of CPCs reflect genomic instability of these tumors, but only partially explain the aggressive clinical course.This retrospective study enrolled 25 pediatric patients with CPC, receiving treatment between January 2009 and June 2022. Molecular-genetic testing was performed for 20 cases with available tumor tissue and encompassed mutational status, chromosomal aberrations, and gene expression profiles. We analyzed several factors presumably influencing the outcomes, including molecular profiles and clinical parameters. The median follow-up constituted 5.2 years (absolute range 2.8-12.6 years).All studied CPCs had smooth mutational profiles with the only recurrent event being TP53 variants, either germline or somatic, encountered in 13 cases. Unbalanced whole-chromosome aberrations, notably multiple monosomies, were highly typical. In 7 tumors, chromosome losses were combined with complex genomic rearrangements: segmental gains and losses or signs of chromothripsis. This phenomenon was associated with extremely low 5-year survival: 20.0 ± 17.9% vs 85.7 ± 13.2%; P = .009. Transcriptomically, the cohort split into 2 polar clusters Ped_CPC1 and Ped_CPC2 differing by survival: 31.3 ± 17.8% vs 100%; P = .012.CPCs split into at least 2 molecular subtypes distinguished both genomically and transcriptomically. Clusterization of the tumors into Ped_CPC1 and Ped_CPC2 significantly correlates with survival. The distinction may prove relevant in clinical trials for dedicated and patient-oriented optimization of clinical protocols for these rare tumors.
Cell-based cccDNA reporter assay combined with functional genomics identifies YBX1 as HBV cccDNA host factor and antiviral candidate target
Authors: Eloi R Verrier, Gaëtan Ligat, Laura Heydmann, Katharina Doernbrack, Julija Miller, Anne Maglott-Roth, Frank Jühling, Houssein El Saghire, Margaux J Heuschkel, Naoto Fujiwara, Sen-Yung Hsieh, Yujin Hoshida, David E Root, Emanuele Felli, Patrick Pessaux, Atish Mukherji, Laurent Mailly, Catherine Schuster, Laurent Brino, Michael Nassal, Thomas F. Baumert
Journal: Gut (2022)

Objectives Chronic hepatitis B virus (HBV) infection is a leading cause of liver disease and hepatocellular carcinoma. A key feature of HBV replication is the synthesis of the covalently close circular (ccc)DNA, not targeted by current treatments and whose elimination would be crucial for viral cure. To date, little is known about cccDNA formation. One major challenge to address this urgent question is the absence of robust models for the study of cccDNA biology. Design We established a cell-based HBV cccDNA reporter assay and performed a loss-of-function screen targeting 239 genes encoding the human DNA damage response machinery. Results Overcoming the limitations of current models, the reporter assay enables to quantity cccDNA levels using a robust ELISA as a readout. A loss-of-function screen identified 27 candidate cccDNA host factors, including Y box binding protein 1 (YBX1), a DNA binding protein regulating transcription and translation. Validation studies in authentic infection models revealed a robust decrease in HBV cccDNA levels following silencing, providing proof-of-concept for the importance of YBX1 in the early steps of the HBV life cycle. In patients, YBX1 expression robustly correlates with both HBV load and liver disease progression. Conclusion Our cell-based reporter assay enables the discovery of HBV cccDNA host factors including YBX1 and is suitable for the characterisation of cccDNA-related host factors, antiviral targets and compounds.
Post COVID-19 irritable bowel syndrome
Authors: Giovanni Marasco, Cesare Cremon, Maria Raffaella Barbaro, Giulia Cacciari, Francesca Falangone, Anna Kagramanova, Dmitry Bordin, Vasile Drug, Egidia Miftode, Pietro Fusaroli, Salem Youssef Mohamed, Chiara Ricci, Massimo Bellini, Mohammed Masudur Rahman, Luigi Melcarne, Javier Santos, Beatriz Lobo, Serhat Bor, Suna Yapali, Deniz Akyol, Ferdane Pirincci Sapmaz, Yonca Yilmaz Urun, Tugce Eskazan, Altay Celebi, Huseyin Kacmaz, Berat Ebik, Hatice Cilem Binicier, Mehmet Sait Bugdayci, Munkhtsetseg Banzragch Yağcı, Husnu Pullukcu, Berrin Yalınbas Kaya, Ali Tureyen, İbrahim Hatemi, Elif Sitre Koc, Goktug Sirin, Ali Riza Calıskan, Goksel Bengi, Esra Ergun Alıs, Snezana Lukic, Meri Trajkovska, Keren Hod, Dan Dumitrascu, Antonello Pietrangelo, Elena Corradini, Magnus Simren, Jessica Sjölund, Navkiran Tornkvist, Uday C Ghoshal, Olga Kolokolnikova, Antonio Colecchia, Jordi Serra, Giovanni Maconi, Roberto De Giorgio, Silvio Danese, Piero Portincasa, Antonio Di Sabatino, Marcello Maggio, Elena Philippou, Yeong Yeh Lee, Daniele Salvi, Alessandro Venturi, Claudio Borghi, Marco Zoli, Paolo Gionchetti, Pierluigi Viale, Vincenzo Stanghellini, Giovanni Barbara
Journal: Gut (2022)

Objectives The long-term consequences of COVID-19 infection on the gastrointestinal tract remain unclear. Here, we aimed to evaluate the prevalence of gastrointestinal symptoms and post-COVID-19 disorders of gut–brain interaction after hospitalisation for SARS-CoV-2 infection. Design GI-COVID-19 is a prospective, multicentre, controlled study. Patients with and without COVID-19 diagnosis were evaluated on hospital admission and after 1, 6 and 12 months post hospitalisation. Gastrointestinal symptoms, anxiety and depression were assessed using validated questionnaires. Results The study included 2183 hospitalised patients. The primary analysis included a total of 883 patients (614 patients with COVID-19 and 269 controls) due to the exclusion of patients with pre-existing gastrointestinal symptoms and/or surgery. At enrolment, gastrointestinal symptoms were more frequent among patients with COVID-19 than in the control group (59.3% vs 39.7%, p&lt;0.001). At the 12-month follow-up, constipation and hard stools were significantly more prevalent in controls than in patients with COVID-19 (16% vs 9.6%, p=0.019 and 17.7% vs 10.9%, p=0.011, respectively). Compared with controls, patients with COVID-19 reported higher rates of irritable bowel syndrome (IBS) according to Rome IV criteria: 0.5% versus 3.2%, p=0.045. Factors significantly associated with IBS diagnosis included history of allergies, chronic intake of proton pump inhibitors and presence of dyspnoea. At the 6-month follow-up, the rate of patients with COVID-19 fulfilling the criteria for depression was higher than among controls. Conclusion Compared with controls, hospitalised patients with COVID-19 had fewer problems of constipation and hard stools at 12 months after acute infection. Patients with COVID-19 had significantly higher rates of IBS than controls. Trial registration number NCT04691895 .
Hepatocyte Ninjurin2 promotes hepatic stellate cell activation and liver fibrosis through the IGF1R/EGR1/PDGF-BB signaling pathway
Authors: Yifan Wang, Pengyun Wang, Yubing Yu, Erwen Huang, Yufeng Yao, Di Guo, Huixin Peng, Beijia Tian, Qian Zheng, Mengru Jia, Jing Wang, Xinna Wu, Jianding Cheng, Huiying Liu, Qing K. Wang, Chengqi Xu
Journal: Metabolism (2022)
Macrophage GSK3β-deficiency inhibits the progression of hepatocellular carcinoma and enhances the sensitivity of anti-PD1 immunotherapy
Authors: Guangshun Sun, Hanyuan Liu, Jie Zhao, Jinyu Zhang, Tian Huang, Guoqiang Sun, Siqi Zhao, Zihao Zhang, Hengsong Cao, Dawei Rong, Xiangyi Kong, Qinghua Ji, Li Liu, Xuehao Wang, Weiwei Tang, Yongxiang Xia
Journal: Journal for ImmunoTherapy of Cancer (2022)

Background Glycogen synthase kinase 3β (GSK3β) was originally discovered to regulate glycogen synthesis and show a relationship to tumors. However, the biological functions of GSK3β in tumor-associated macrophages (TAMs) in cancers including hepatocellular carcinoma (HCC) remain unclear. Methods The enrichment of GSK3β in tumor tissues was assessed by Gene Expression Omnibus (GEO) database. The in vitro and in vivo assays assisted in evaluating how GSK3β in TAMs affected HCC in terms of proliferation, invasion and migration. Immunofluorescence was used to assess GSK3β expression in TAMs in the anti-PD1 therapy non-responsive HCC group and the responsive group. Western blot and coimmunoprecipitation were performed to demonstrate the interaction between GSK3β and PD-L1. We carried out in vivo experiments in a C57BL/6 mouse model of HCC established through subcutaneous injection. Results GEO single-cell RNA sequencing data suggested that GSK3β was highly enriched in TAMs of HCC. According to in vitro and in vivo experiments, reducing GSK3β in TAMs inhibits the cancer cell proliferation, invasion, and migration. The immunofluorescence and immunohistochemistry results confirmed that the GSK3β is significantly upregulated in TAMs of the anti-PD1 therapy non-responsive group in comparison with the responsive group. In vitro and in vivo experiments confirmed that reduced GSK3β in TAMs are capable of enhancing the sensitivity of anti-PD1 immunotherapy for HCC by decreasing PD-L1 ubiquitination. Mass spectrometry results suggested that high expression of CD14 + GSK3β + in the peripheral blood mononuclear cell (PBMC) can predict non-responsive to anti-PD1 treatment. Moreover, escitalopram is confirmed to act as GSK3β inhibitor that can increase the sensitivity of anti-PD1 immunotherapy for HCC. Conclusions This study revealed that macrophage GSK3β deficiency can inhibit the development of HCC by inhibiting the M2 phenotype and enhance the sensitivity of anti-PD1 immunotherapy for HCC by decreasing PD-L1 ubiquitination. The expression of CD14 + GSK3β + in PBMC can noninvasively predict anti-PD1 sensitivity in HCC patients, which provides novel strategies to predict anti-PD1 sensitivity, increase anti-PD1 therapeutic effect, and bring new hope for HCC patients.
Solvent-associated olfactory dysfunction: not a predictor of deficits in learning and memory
Authors: B S Schwartz, D P Ford, K I Bolla, J Agnew, M L Bleecker
Journal: American Journal of Psychiatry (1991)

The aim of the study was to evaluate associations between olfactory dysfunction and aberrations in learning and memory after chronic occupational exposure to mixed hydrocarbon solvents.This was a cross-sectional, epidemiologic study of 187 paint manufacturing workers. The authors administered quantitative tests of olfactory function (the University of Pennsylvania Smell Identification Test) and neurobehavioral function (eight computer- and examiner-administered tests of learning and memory) to workers for whom detailed information was available on lifetime occupational exposure to solvents.Olfactory function test scores were positively correlated with performance on seven of eight of the tests of learning and memory in bivariate analyses. After adjustment for important confounding variables (i.e., age, vocabulary score, and cumulative exposure to hydrocarbon solvents) with multiple linear regression, olfactory function scores predicted performance only on the Wechsler Memory Scale Delayed Logical Memory test.Overall, the data did not reveal that olfactory dysfunction was correlated with decrements in various memory functions.
Frontline Promise for Adagrasib–Pembrolizumab Combination
Journal: Cancer Discovery (2022)

Two trials offer early evidence that adagrasib plus pembrolizumab is a safe and effective regimen for patients with newly diagnosed non-small cell lung cancer harboring a KRASG12C mutation. The overall response rate in one trial was 49%, and in the other it was 57%. The drug combination showed lower levels of liver toxicity than other combinations of checkpoint inhibitors and targeted therapies.
The NHS can lead the way for staff receiving fertility treatment
Authors: Roshani Patel
Journal: BMJ (2022)

The NHS can lead the way for staff receiving fertility treatment Roshani Patel ST6 general surgery and research fellow 1, 2 Society and the National Health Service have been failing patients requiring fertility treatment.I know this all too well as both a doctor and patient with infertility.These failures manifest in unfair access to treatment and misinformed attitudes, which see people refuse to accept infertility as a treatable disease.
Ca Minerals and Oral Bioavailability of Pb, Cd, and As from Indoor Dust in Mice: Mechanisms and Health Implications
Authors: Hong-Bo Li, Rong-Yue Xue, Xiao-Qiang Chen, Xin-Ying Lin, Xiao-Xia Shi, Hai-Yan Du, Nai-Yi Yin, Yan-Shan Cui, Li-Na Li, Kirk G. Scheckel, Albert L. Juhasz, Xi-Mei Xue, Yong-Guan Zhu, Lena Q. Ma
Journal: Environmental Health Perspectives (2022)

Elevating dietary calcium (Ca) intake can reduce metal(loid)oral bioavailability. However, the ability of a range of Ca minerals to reduce oral bioavailability of lead (Pb), cadmium (Cd), and arsenic (As) from indoor dust remains unclear.
Annals Consult Guys - Postoperative Atrial Fibrillation
Authors: Howard H. Weitz, Geno J. Merli, Konstantinos Siontis
Journal: Annals of Internal Medicine (2022)

Web ExclusivesDecember 2022Annals Consult Guys - Postoperative Atrial FibrillationFREEHoward H. Weitz, MD, Geno J. Merli, MD, and Konstantinos Siontis, MDHoward H. Weitz, MDThomas Jefferson University, Philadelphia, Pennsylvania (H.H.W., G.J.M.)Search for more papers by this author, Geno J. Merli, MDThomas Jefferson University, Philadelphia, Pennsylvania (H.H.W., G.J.M.)Search for more papers by this author, and Konstantinos Siontis, MDMayo Clinic, Rochester, Minnesota (K.S.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/W21-0013 CME/MOC SectionsSupplemental MaterialAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail The Annals Consult Guys help listeners think through the evaluation and management of a patient with postoperative atrial fibrillation. Is it a benign condition or one that signals risks for future problems?For more videos from and information on Annals Consult Guys, visit go.annals.org/ConsultGuys. Comments0 CommentsSign In to Submit A Comment Joseph Jumao-asInspira Health New Jersey25 January 2023 Post Op Atrial Fibrillation Excellent presentation as always. I'm wondering if there are data about minor outpatient surgical procedure and complicated by Atrial Fibrillation. Author, Article, and Disclosure InformationAffiliations: Thomas Jefferson University, Philadelphia, Pennsylvania (H.H.W., G.J.M.)Mayo Clinic, Rochester, Minnesota (K.S.)Disclosures: Drs. Merli and Weitz report that they have no financial relationships or interests to disclose. Dr. Siontis is a co-inventor of an Al ECG technology that is licensed to Anumana, Inc., with potential for commercialization. All relevant financial relationships have been mitigated. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=W21-0013.Editors' Disclosures: The editors have no relevant financial relationships to disclose. Individual forms may be viewed at www.annals.org/editorsdisclosures. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics December 2022Volume 175, Issue 12Page: CG1 ePublished: 20 December 2022 Issue Published: December 2022 Copyright & PermissionsCopyright © 2022 by American College of Physicians. All Rights Reserved.Loading ...